Abstract:
:The cholinergic hypothesis of memory dysfunction has guided most of the recent proposals for treating the primary symptoms of AD. The efficacy of these treatments has been severely limited. This review examines two major lines of evidence which suggest that the cholinergic hypothesis may have to be expanded and revised. The cholinergic hypothesis focuses on pre-synaptic defects. It assumes cholinoceptive neurons would function normally with adequate stimulation. Evidence is not sufficient to support this assumption. In addition, dissociations have been demonstrated between muscarinic receptor number and functional response of cholinoceptive neurons. Various measures are proposed to investigate the functional integrity of muscarinic receptors in AD patients. AD often has been characterized as a disorder produced by generalized cholinergic hypoactivity. Evidence for cortisol hypersecretion, abnormal dexamethasone suppression, and the occurrence of depressive symptoms, motoric dysfunction and sleep abnormalities in AD patients is more consistent with regional cholinergic hyperactivity than generalized hypoactivity. Resolution of these discrepancies could shed new light on the pathophysiology and treatment strategies for AD. Cholinoceptive neurons could be hypersensitive, subsensitive or have unaltered responsivity. These options would have very different treatment implications. New developments in outcome assessment which are capable of discriminating varieties of differential response to treatment can spur treatment development and improve quality of care for patients with complex disorders such as AD.
journal_name
Prog Neuropsychopharmacol Biol Psychiatryauthors
Pomara N,Bagne CA,Stanley M,Yarbrough GGdoi
10.1016/0278-5846(86)90025-4subject
Has Abstractpub_date
1986-01-01 00:00:00pages
553-69issue
3-5eissn
0278-5846issn
1878-4216journal_volume
10pub_type
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
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journal_title:Progress in neuro-psychopharmacology & biological psychiatry
pub_type: 杂志文章,评审
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